Overview:
Formerly known as Pneumocystis carinii,
and classified as a protozoa, investigative
tests upon this organism’s nucleic acid and
biochemical composition has since placed it in
the Kingdom of Fungi. Pneumocystis jiroveci
is found in the lungs of mammals, where it
resides in the alveoli without causing overt
infection until the host's immune system becomes
debilitated, causing the fungal infection
Pneumocystis
pneumonia or
pneumocystosis.
Thus, the organism causes disease in
immunosuppressed individuals, including those
with AIDS or undergoing chemotherapeutic
treatments. P. jiroveci is specific to
humans; it has not been shown to infect other
animals, while other species of Pneumocystis
that parasitize other animals have not been
shown to infect humans.

Figure 1.
This photomicrograph reveals Pneumocystis
jirovecii fungi, which were present in this
Giemsa-stained impression smear of rat lung
tissue. Note the round cyst in the very middle
of this image containing eight immature haploid
neuclei, as well as numbers of freed
trophozoites [1000 X].

Biology: P. jiroveci is a non-motile unicellular
eukaryote, traditionally described in two
different forms. The small trophic forms 1 μm
(micrometres) to 5 μm in size are pleomorphic
and ameboid in shape, generally represent the
majority of organisms identified in the lungs of
animals with P. jiroveci pneumonia, and
frequently exist as large clusters. The larger
cyst forms 5 μm to 8 μm in diameter are the most
readily recognized forms of the organism,
although representing only a small percentage of
organisms in the lungs of animals with P.
jiroveci pneumonia. The smooth spherical
cyst form is enclosed by a thick cell wall and
may contain up to eight intracystic bodies
(sporozoites). These intracystic bodies may
represent precursors to tropic forms which may
develop upon release by the cyst, although the
life-cycle has not been established and is
poorly understood.

Life Cycle:
In the asexual phase, trophic forms replicate by
mitosis. In the sexual phase, haploid trophic
forms conjugate and produce a zygote or
sporocyte (early cyst) (Figure 2). The zygote
undergoes meiosis and subsequent mitosis to
produce eight haploid nuclei (late phase cyst).
Spores exhibit different shapes (such as,
spherical and elongated forms). It is postulated
that elongation of the spores precedes release
from the spore case. It is believed that the
release occurs through a hole in the cell wall.
After release, the empty spore case usually
collapses, but retains some residual cytoplasm.
A trophic stage, where the organisms probably
multiply by binary fission is also recognized to
exist.

Figure 2. Pneumocystis jiroveci cysts.

Virulence and
Pathogenicity: The attachment of P.
jiroveci to lung epithelial cells, upon
inhalation of the trophozoite (replicating)
form, appears to be a critical step in
establishing disease in the susceptible host.
Attachment to lung epithelial cells (type I
pneumocytes) may be mediated in part by
a variety of host molecules, including
fibronectin, vitronectin, laminin, and mannose
receptors. Type I pneumocytes (squamous alveolar
cells) are responsible for gas exchange in the
alveoli and cover a majority of the alveolar
surface area (>95%). Binding may be facilitated
by P. jiroveci extracellular matrix
receptors. In the susceptible host, attachment
of P. jiroveci to alveolar epithelial
cells is associated with proliferation of the
organism and impaired lung cell replication,
perhaps through secretion of proteolytic enzymes
such as chymase or reactive oxygen species
(Patel & Koziel, 2004).

Although specific virulence
factors are poorly defined, P. jiroveci
can induce disease in the susceptible host
through a number of strategies. P. jiroveci
induces selective alterations in expression and
biophysical activity of lung surfactants, and
may also have effects on non-epithelial lung
cells such as alveolar macrophages and lung
monocytes by down-regulation of important cell
transcription factors. By coating itself in
host-derived glycoprotein molecules from the
lung microenvironment such as surfactant
protein-A and a soluble form of the macrophage
mannose receptor, P. jiroveci may delay
recognition and destruction by the host immune
system, to enable proliferation and survival
(Patel & Koziel, 2004).

P. jiroveci
replicates extracellularly and impairs oxygen
diffusion. Inflammation induced by this pathogen
causes host cell damage, resulting in cell lysis
and rupture. Damage to the lung basement
membrane generates a characteristic foamy
exudate and
interstitial leukemic infiltration
in the
alveoli, thereby reducing alveolar
capillary permeability. Granulomatous
inflammation in Pneumocystis pneumonia
is rare but may be seen in up to 5% of lung
biopsies from human immunodeficiency virus
(HIV)-infected patients.

Identification:
Prior to the mid-1990s, the only way of
detecting the presence of a Pneumocystis
infection was through the visualization of the
fungal microbe from stained respiratory tissues
using Giemsa and Gomori-Grocott techniques,
staining sputum, branchoalveolar fluid or lung
tissue (Thomas et al., 2004). When
staining, the firm-walled cyst form is most
visible, but the flexible-walled trophic form
outnumbers the cyst form 1:10 and the trophic
form is difficult to visualize (Forbes et al.,
2003). Therefore, staining is not the most
convenient way of detecting infection.
Polymerase chain reaction (PCR) is now used to
identify the presence of the organism in medical
specimens, which has increased the sensitivity
of detecting the microbe.

Clinical Infections: In
individuals with AIDS, highly active
antiretroviral therapy (HAART) is the most
common treatment, which also reduces the death
and infection with opportunistic microbes. The
infection occurs more frequently when the
concentration of T helper cells is below 200
cells per cubic millimeter. In fact, a low T
helper cell count can impair hydrogen peroxide
and superoxide production by alveolar
macrophages. In healthy individuals, P.
jiroveci is cleared from the lungs via
phagocytosis by alveolar macrophages. It is
believed that immune cells recognize the
pathogen by the mannose-containing residues. The
symptoms of a pneumocystis pneumonia include
progressive dyspnea, nonproductive cough, and
low grade fever.

Treatment:
Antifungal medications do not kill P.
jiroveci. The antibiotic
Trimethoprim-sulfamethoxazole is the primary
treatment for all severity of pneumocystis
pneumonia. Trimethoprim is an inhibitor of
dihydrofolate reductase and sulfamethoxazole is
an inhibitor of dihydropteroate synthase. The
microbe stays within hosts for weeks after
therapy has begun. It is of extreme importance
that patients with AIDS take the preventative
methods to avoid pneumocystis pneumonia because
without treatment, over 85% of people with HIV
develop the infection (Stringer et al.,
2002).